Dexmedetomidine Alleviates Hyperoxia-Induced Acute Lung Injury via Inhibiting NLRP3 Inflammasome Activation

Abstract

Background/Aims: Dexmedetomidine (Dex), a specific agonist of α2-adrenoceptor, has been reported to have extensive pharmacological effects. In this study, we focused on the protective effect of Dex on hyperoxia-induced acute lung injury and further explored its possible molecular mechanisms. Methods: The model of hyperoxia-induced acute lung injury was established by continuous inhalation of oxygen (FiO2= 0.90) for 7 d in neonatal rats in vivo. The in vitro experiments were carried out in LPS/ATP or hyperoxia-treated RAW264.7 cells. ELISA, western blot, TUNEL staining, and immunohistochemistry staining assays were performed and the commercial kits were used to assess the beneficial effect of Dex on hyperoxia-induced acute lung injury. Results: According to our results, Dex treatment attenuated hyperoxia-induced acute lung injury via decreasing the lung wet/dry(W/D) weight ratio and mitigating pathomorphologic changes. Moreover, the oxidative stress injury, inflammatory reaction, and apoptosis in lung epithelial cells were inhibited by Dex treatment. In addition, the activation of NLRP3 inflammasome was restrained by Dex both in lung tissue in vivo and RAW264.7 cells in vitro. Conclusion: These data provide evidence that Dex may ameliorate hyperoxia-induced acute lung injury, which suggests a potential clinical application of Dex in long-term supplemental oxygen therapy.

Dexmedetomidine alleviates lipopolysaccharide‐induced acute kidney injury by inhibiting the NLRP3 inflammasome activation via regulating the TLR4/NOX4/NF‐κB pathway

“…In the current study, we measured the expression of NLRP3 inflammasome associated proteins and the results suggested LPS significantly increased these proteins expression and subsequent upregulated the secretion of IL‐1β and IL‐18 inflammatory factors, while DEX significantly reduced their expression. Similarly, the same effect of DEX was confirmed in acute lung injury induced by hyperoxia . These results confirmed that DEX inhibits the activation of NLRP3 inflammasome induced by LPS in kidney.…”

Cathepsin B-Mediated NLRP3 Inflammasome Formation and Activation in Angiotensin II -Induced Hypertensive Mice: Role of Macrophage Digestion Dysfunction

“…The NLRP3 inflammasome plays a critical role in the development of different types of chronic diseases, such as vascular diseases, aging, and chronic infections [32][33][34]. Through various approaches, we confirmed that Ang II stimulation induced the formation and activation of the NLRP3 inflammasome complex in cultured macrophages, as shown using confocal microscopy by colocalization of NLRP3 with ASC or caspase-1 and by biochemical analysis of caspase-1 activity (Fig.…”

Renoprotective effects Of Dexmedetomidine against ischemia-reperfusion injury in streptozotocin-induced diabetic rats

“…Although DEX renoprotective effects against IR injury in diabetic rats are achieved by ameliorating lipid peroxidation and oxidative stress[7], present study is the first to demonstrate that protective effects of DEX against renal IR injury in diabetic rats are associated with the inhibition of inflammasome. This result is consistent with recent studies with non-diabetic animal models that demonstrated that DEX reduces inflammasome activation [17]. DEX ameliorated IR-induced increase in phospho-AKT and phospho-ERK compared to D-IRC group levels and IR-induced decrease in anti-apoptotic Bcl-2 and pro-apoptotic Bax levels.…”